This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of this project was to elucidate the cellular targets of stress exerted by copper (Cu) surfaces. Prior to this work it was not known if the antimicrobial properties of Cu surfaces are directly related to cell wall or membrane damage, release of Cu ions with concomitant Cu uptake and copper poisoning of the cells. Alternatively, the underlying mechanisms could be degradation of genetic material or that bacteria die by indirect oxidative events caused by Cu. Specifically the following potential modes of Cu surface stress were investigated in this project: (i) membrane damage, (ii) mutagenicity of DNA and (iii) oxidative damage. To address these questions we have pursued two independent strategies: Aim 1: Identify the molecular targets that govern inactivation of bacteria such as Escherichia coli and fungi such as the yeasts Saccharomyces cerevisiae or Candida albicans on metallic Cu surfaces. Aim 2: Identify genetic factors responsible for resistance against metallic copper surfaces. Overall, these studies have improved our understanding of Cu surface mediated toxicity and of the underlying mode of antimicrobial action of metallic Cu.